The following description summarizes information relevant to the present invention. It is not an admission that any of the information provided herein is prior art to the presently claimed invention, nor that any of the publications specifically or implicitly referenced are prior art to that invention.
Publications and other materials including patents and patent applications used to explain the specification are hereby incorporated by reference.
Cannabinoids include a group of terpenophenolic compounds present in Cannabis (Cannabis sativa). More broadly, the term relates to a group of substances that are structurally related to tetrahydrocannabinol (THC) or that bind to cannabinoid receptors.
Endocannabinoids are substances produced from within the body which also activate cannabinoid receptors. The first endocannabinoid that was identified was arachidonoyl ethanolamide (AEA). Another endocannabinoid that has been identified is 2-arachidonoyl glycerol (2-AG). Like Δ9-tetrahydrocannabinol, many of the actions of AEA and 2-AG are mediated through the cannabinoid receptors CB1 and CB2.
Cannabinoids have broad effects on the central nervous system (CNS) and influence, for example, movement, memory, nociception, endocrine regulation, thermoregulation, sensory perception, cognitive functions, and mood. Similarly, genetic and pharmacological studies have revealed a broad role for endocannabinoid signaling in a variety of physiological processes, including neuromodulator release, motor learning, synaptic plasticity, appetite, and pain sensation.
Overall, the effects of cannabinoids and endocannabinoids correlate with the distribution of CB1, one of the most abundant G-protein-coupled receptors in the central nervous system. Knockout CB1 and CB2 mice confirm the important role of the cannabinoid system (and by inference the endocannabinoids) in the above physiological responses as well as in mediating opiate addictive behavior, learning, and immunological responses.
In the CNS, the endocannabinoids AEA and 2-AG are believed to be synthesized on demand by postsynaptic neurons and to serve as retrograde neurotransmitters to presynaptically localized CB1. As with any other neurotransmitter, there are specific mechanisms for the inactivation of endocannabinoids. The inactivation of AEA occurs within cells and is primarily facilitated by the enzyme ‘anandamide amidase’, now known as FAAH, which hydrolysis AEA into arachidonic acid and ethanolamine. By metabolizing anandamide, FAAH maintains an inward concentration gradient that drives AEA's cellular accumulation. FAAH is expressed throughout the mammalian central and peripheral nervous systems and in many organs, including brain, spinal cord, liver, testis, kidney, retina, uterus, and placenta. It is usually found post synaptically in cell bodies.